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Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer

INTRODUCTION: Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However,...

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Autores principales: Zhang, Xiaofang, Wu, Xiaojuan, Su, Peng, Gao, Yongsheng, Meng, Bin, Sun, Yanlin, Li, Li, Zhou, Zhiqiang, Zhou, Gengyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487728/
https://www.ncbi.nlm.nih.gov/pubmed/23133636
http://dx.doi.org/10.1371/journal.pone.0048492
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author Zhang, Xiaofang
Wu, Xiaojuan
Su, Peng
Gao, Yongsheng
Meng, Bin
Sun, Yanlin
Li, Li
Zhou, Zhiqiang
Zhou, Gengyin
author_facet Zhang, Xiaofang
Wu, Xiaojuan
Su, Peng
Gao, Yongsheng
Meng, Bin
Sun, Yanlin
Li, Li
Zhou, Zhiqiang
Zhou, Gengyin
author_sort Zhang, Xiaofang
collection PubMed
description INTRODUCTION: Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer; METHODS: We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected; RESULTS: DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERα-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited. CONCLUSIONS: In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells.
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spelling pubmed-34877282012-11-06 Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer Zhang, Xiaofang Wu, Xiaojuan Su, Peng Gao, Yongsheng Meng, Bin Sun, Yanlin Li, Li Zhou, Zhiqiang Zhou, Gengyin PLoS One Research Article INTRODUCTION: Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer; METHODS: We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected; RESULTS: DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERα-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited. CONCLUSIONS: In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells. Public Library of Science 2012-11-02 /pmc/articles/PMC3487728/ /pubmed/23133636 http://dx.doi.org/10.1371/journal.pone.0048492 Text en © 2012 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Xiaofang
Wu, Xiaojuan
Su, Peng
Gao, Yongsheng
Meng, Bin
Sun, Yanlin
Li, Li
Zhou, Zhiqiang
Zhou, Gengyin
Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer
title Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer
title_full Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer
title_fullStr Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer
title_full_unstemmed Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer
title_short Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer
title_sort doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487728/
https://www.ncbi.nlm.nih.gov/pubmed/23133636
http://dx.doi.org/10.1371/journal.pone.0048492
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